Cyanoguanidine derivatives

ABSTRACT

Novel cyanoguanidine derivatives, and acid addition salts thereof useful as medicines which have pharmacological actions such as anti-secretory effect, local anesthesia action and the like; and process for the preparation thereof.

This application is a divisional application of application Ser. No.178,017, filed Aug. 13, 1980 (now U.S. Pat. No. 4,327,217), whichapplication is in turn a divisional application of application Ser. No.120,876, filed Feb. 12, 1980 (now U.S. Pat. No. 4,287,346).

This invention relates to novel cyanoguanidine derivatives, acidaddition salts thereof having excellent actions as medicines and to theprocess for the preparation thereof, wherein the cyanoguanidinederivatives are represented by the general formula: ##STR1## wherein Arepresents a substituted or unsubstituted phenyl, furyl, thienyl orcycloalkyl group;

B represents pyridyl, phenyl, or pyridine-N-oxide group;

R represents a lower alkyl group, a lower alkenyl group, or a group ofthe formula: ##STR2## wherein R₁ and R₂ are the same or different, andeach represent a lower alkyl group, or together form nitrogen-containingheterocycle with the nitrogen atom to which they bond, and n is aninteger of 1-3, or R represents a group of the formula: ##STR3## whereinR₃ is a lower alkyl group, n is an integer of 1-3 and m is an integer of4-5;

X represents an alkylene or an alkylene group containing the terminalsulfur atom; and

p is 0 or 1, with the proviso that (i) when A is unsubstituted phenyland B is pyridyl, p is 1 and R is a group of the formula: ##STR4## or agroup of the formula: ##STR5## and (ii) when A is unsubstituted phenyland B is phenyl or pyridine-N-oxide, p is 0; and intermediate thereforrepresented by the general formula: ##STR6## wherein Y represents alower alkoxy or a lower alkylthio group, and A, B, X and p have the samemeanings as defined above.

Illustrative substituents on the substituted phenyl groups mentioned forthe definition of A in the general formula (I) include, practically, alower alkyl, lower alkenyl, halogen, lower alkoxy, lower alkylthio,lower alkylsulfonyl, halogen substituted lower alkyl groups and thelike. The term "lower" used in the above illustration is meant for anystraight or branched carbon chains containing 1-6 carbon atoms.Illustrative said lower alkyl groups may include, for example, methyl,ethyl, n-propyl, isopropyl, isobutyl, 1-methylpropyl, tert-butyl,n-pentyl, 1-ethylpropyl, isoamyl, n-hexyl and the like, and loweralkenyl groups may include isopropenyl, allyl, crotyl, methallyl and thelike.

The lower alkoxy or a lower alkylthio group mentioned for the definitionof Y in the general formula (V) has also 1-6 carbon atoms.

The term "halogen" means practically fluoro, chloro, iodo or bromogroup.

The cycloalkyl group means practically a cycloalkyl group containing 5-6carbon atoms. The lower alkyl and lower alkenyl groups shown in thedefinitions of R, R₁ and R₂ have the same meanings as those definedabove.

Further, illustrative nitrogen-containing heterocycles formed by thegroups R₁ and R₂, with nitrogen atom to which they bond, include, forexample, pyrrolidine, piperidine, piperazine, morpholine and the like.

Alkylene represented by X means lower alkylene groups, such, forexample, as methylene, ethylene, propylene, and the like, which maycontain a terminal sulfur atom. The pyridyl group represented by B maybe combined at any one of the 2, 3 and 4 positions on the pyridine ring.

There are some tautomers of the compound (I) of this invention, andthese tautomers are, of course, included in this invention.

The compound (I) of this invention may be easily converted into thepharmacologically acceptable acid addition salt by reacting it with aninorganic or organic acid. Illustrative inorganic acids includehydrochloric, hydrobromic, hydroiodic, sulfuric acids and the like, andillustrative organic acids include maleic, fumaric, succinic, acetic,malonic, citric, benzoic acids and the like.

The compounds to be provided according to this invention are all novelcompounds which have not as yet been reported in the literature. Saidcompounds have very excellent and broad pharmacological actions asmedicine, such as, very intensively, gastric juice secretion inhibitoryor antisecretory, antidepressant, local anesthesia, antidiarrheal,antiedema, diuretic, hypertensive, hypotensive, vasoconstrictive,antiserotonin, smooth muscle relaxing, coronary vasodilative, andbradycardia actions and the like. Thus, the compounds (I) of thisinvention are useful as various medicines due to such pharmacologicalactions. Illustrative medicines include antipeptic ulcer drug,antidepressant, local anesthetics, anti-inflammatory agents, diuretics,antiallergic agents, antidiarrheal, hypertensive, hypotensive,anti-arrhythmic agent, muscle relaxants, coronary vasodilator and thelike.

Since the inhibitory action of the compounds according to this inventionto gastric juice secretion is not based on the anticholine action, thecompound of this invention do not exhibit the side effect due to theanticholine action. This is a great characteristic of the compoundsaccording to this invention, and therefore the compounds areparticularly expected as a new type antipeptic ulcer drug among thevarious medicines mentioned above.

The compounds (I) of this invention can be prepared through variousprocesses. Among these processes, the following shows one process whichmay be usually employed. ##STR7## wherein Y represnts a lower alkoxy ora lower alkylthio group, and A, B, R, X and p have the same meanings asdefined above.

Process (1) for the Preparation

The compounds (I) of this invention are produced, in one step, byreacting the amine derivative represented by the above formula (II) withan isothiourea derivative or an isourea derivative represented by theabove formula (III). This reaction may be effected in the presence orabsence of solvent.

An excess amount of the amine derivative may be used as a solvent.However, it is desirable to use, for example, methanol, ethanol,isopropanol, acetonitrile, chloroform and the like as solvent. Thereaction is effected at room temperature or elevated temperature. Thereaction may be effected under reflux, when solvent is used.

Process (2) for the Preparation

The compounds represented by the general formula (I) of this inventionare produced, through two steps, by reacting the amine derivativerepresented by the general formula (II) with a compound represented bythe general formula (IV) to produce a compound represented by thegeneral formula (V), followed by reacting the latter compound (V) withan amine represented by the general formula (VI). According to thisprocess, both reactions of said two steps may be effected with thesimilar procedures as the reaction between the amine derivative (II) andthe isothiourea derivative or isourea derivative (III) as describedabove. This reaction may be also effected without separating thecompound (V) from the reaction vessel after the reaction of the aminederivative (II) with the compound (IV).

The excellent pharmacological actions of the compounds of this inventionare illustrated hereinafter with respect to typical compounds of thisinvention.

1. Anti-secretory effect

Inhibitory ratio to the gastric juice serection was determined by theShay rat 4 hr method [H. Shay et al.; Gastroentrogy, vol. 5, P. 43(1945)]. Results are shown in Table 1.

                  TABLE 1                                                         ______________________________________                                                              Oral                                                                          dosage   Inhibitory                                     Compound              (mg/Kg)  ratio (%)                                      ______________________________________                                        Known   Cimetidine                                                            compound                                                                              (control)         50       85.8                                               N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)benzyl]                                                   guanidine (control)                                                                             100      69.3                                       Compound                                                                              N--cyano-N'--ethyl-N--                                                of this [α-(2-pyridyl)ortho-                                            invention                                                                             methylbenzyl]                                                                 guanidine         50       93.5                                               N--cyano-N'--allyl-N--                                                        [α-(2-pyridyl)ortho-                                                    methylbenzyl]                                                                 guanidine         50       79.0                                               N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)ortho-                                                    methoxybenzyl]                                                                guanidine         50       91.6                                               N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)ortho-                                                    methoxybenzyl]                                                                guanidine         50       96.7                                               N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)metha-                                                    chlorobenzyl]                                                                 guanidine         50       79.2                                               N--cyano-N'--(3-diethyl-                                                      aminopropyl)-N--[α-(2-                                                  pyridyl)benzyl]                                                               guanidine         100      81.0                                               N--cyano-N'--(1-ethyl                                                         pyrrolyl-2)-methyl-N--                                                        [α-(2-pyridyl)benzyl]                                                   guanidine         100      86.0                                       ______________________________________                                    

2. Anti-depressant efficacy

Anti-depressant efficacy was determined using mouse by the method asdescribed in G. Chen and B. Bohner: J. Pharmac. Exptl. Therap. 131, 179(1961).

Results are shown in Table 2.

                  TABLE 2                                                         ______________________________________                                                              Minimum effective                                                             dose (mouse, oral                                              Compound       dosage mg/Kg)                                           ______________________________________                                        Known    Imipramine                                                           compound (control)        10                                                           N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)benzyl/                                                   guanidine (control)                                                                            25                                                  Compound N--cyano-N'--ethyl-N--                                               of this  [α-(2-pyridyl)ortho-                                           invention                                                                              methylbenzyl]                                                                 guanidine        1                                                            N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)metha-                                                    methylbenzyl]                                                                 guanidine        10                                                           N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)ortho-                                                    methoxybenzyl]                                                                guanidine        10                                                           N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)ortho-                                                    chlorobenzyl]                                                                 guanidine        10                                                           N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)metha-                                                    chlorobenzyl]                                                                 guanidine        2.5                                                 ______________________________________                                    

3. Local anesthesia action

Local anesthesia action was determined by the method as described in M.R. A. Chance et al., J. Pharmac. Exptl. Therap. 82, 203 (1944). Resultsare shown in Table 3.

                  TABLE 3                                                         ______________________________________                                                              Minimum effective                                              Compound       concentration (%)                                       ______________________________________                                        Known    Dibucaine                                                            compound (control)        0.1                                                          N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)benzyl]                                                   guanidine (control)                                                                            >3                                                  Compound N--cyano-N'--(1-ethyl-                                               of this  pyrolidyl-2)methyl-N--                                               invention                                                                              [α-(2-pyridyl)para-                                                     methylbenzyl]                                                                 guanidine        0.5                                                          N--cyano-N'--(3-dimethyl-                                                     aminopropyl)-N--[α-(2-                                                  pyridyl)paramethylbenzyl]                                                     guandine         0.5                                                          N--cyano-N'--(1-ethylpyro-                                                    lidyl-2)methyl-N--[α-(2-                                                pyridyl)orthomethoxy-                                                         benzyl]guanidine 0.25                                                ______________________________________                                    

4. Antidiarrheal action

                  TABLE 4                                                         ______________________________________                                                              Minimum effective                                                             dose (mouse, oral                                              Compound       dosage, mg/Kg)                                          ______________________________________                                        Known    Atropine                                                             compound (control)        60                                                           N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)benzyl]                                                   guanidine (control)                                                                            50                                                  Compound N--cyano-N'--ethyl-N--                                               of this  [α-(2-pyridyl)ortho-                                           invention                                                                              methylbenzyl]                                                                 guanidine        1                                                            N--cyano-N'--allyl-N--                                                        [α-(2-pyridyl)ortho-                                                    methylbenzyl]                                                                 guanidine        10                                                           N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)ortho-                                                    chlorobenzyl]                                                                 guanidine        5                                                            N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)metha-                                                    chlorobenzyl]                                                                 guanidine        10                                                           N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)metha-                                                    trifluoromethylbenzyl]                                                        guanidine        25                                                  ______________________________________                                    

5. Antiedema action

Antiedema action was determined using rat by the method as described C.A. Winter, et al.: Proc. Soc. Exp. Biol. Med. 111, 544 (1962). Resultsare shown in Table 5.

                  TABLE 5                                                         ______________________________________                                                              Minimum effective                                                             dose (rat, oral                                                Compound       dosage, mg/Kg)                                          ______________________________________                                        Known    Indomethacin                                                         compound (control)        '- N--cyano-N'--methyl-N--                                   [α-(2-pyridyl)benzyl]                                                   guanidine (control)                                                                            >100                                                Compound N--cyano-N'--methyl-N--                                              of this  [α-(2-pyridyl)ortho-                                           invention                                                                              methylbenzyl]                                                                 guanidine        2.5                                                          N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)ortho-                                                    methylbenzyl]                                                                 guanidine        2.5                                                          N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)ortho-                                                    methoxybenzyl]                                                                guanidine        2.5                                                 ______________________________________                                    

6. Diuretics action

Diuretics action was determined by the method as described in E.Cornish: J. Pharm. Pharmacol. 18, 65 (1966). Results are shown in Table6.

                  TABLE 6                                                         ______________________________________                                                              Minimum effective                                                             dose (oral dosage                                              Compound       mg/Kg)                                                  ______________________________________                                        Known    Hydrofulumethiazide                                                  compound (control)        2.0                                                          N--cyano-N'--methyl-N--                                                       [α-(2-pyridyl)benzyl]                                                   guanidine (control)                                                                            5.0                                                 Compound N--cyano-N'--ethyl-N--                                               of this  [α-(2-pyridyl)ortho-                                           invention                                                                              methylbenzyl]                                                                 guanidine        0.1                                                          N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)metha-                                                    methylbenzyl]                                                                 guanidine        0.25                                                         N--cyano-N'--ethyl-N--                                                        [α-(2-pyridyl)metha-                                                    chlorobenzyl]                                                                 guanidine        0.5                                                          N--cyano-N'--methyl-N--                                                       [α(2-pyridyl)metha-                                                     trifluoromethylbenzyl]                                                        guanidine        0.5                                                          N--cyano-N'--allyl-N--                                                        [α-(2-pyridyl)ortho-                                                    methoxybenzyl]                                                                guanidine        1.0                                                 ______________________________________                                    

As apparently seen from the results of the above pharmacologicalexperiments, the guanidine derivatives provided according to thisinvention exhibit very intense pharmacological actions, as compared withthe known compounds.

This invention will be more particularly illustrated by the followingexamples. However, it should be understood that this invention is notlimited to only those examples.

EXAMPLE 1 N-cyano-N'-methyl-N-[α-(2-pyridyl)-o-methylbenzyl]guanidine

(1) (a) Dimethylcyanodithioimido carbonate in amount of 11.4 g (0.1 mol)and α-(2-pyridyl)-o-methylbenzylamine in amount of 18.4 g (0.1 mol) weredissolved in 300 ml of ethanol. The whole was allowed to react at roomtemperature overnight. Crystals deposited were separated by filtration.The filtrate was concentrated to deposit an additional amount ofcrystals. These crystals were combined and recrystallized from ethylacetate to produce 17.7 g (yield: 66.4%) ofN-cyano-S-methyl-N-[α-(2-pyridyl)orthomethylbenzyl]isothiourea.

Melting point: 162°-4° C.

Elementary analysis of the compound having the presumed formula C₁₆ H₁₆N₄ S gave:

    ______________________________________                                                   C          H      N                                                ______________________________________                                        Calculated (%):                                                                            64.83        5.44   18.90                                        Found (%):   65.03        5.31   18.79                                        ______________________________________                                    

(b) A mixture consisting of 5.9 g (0.02 mol) ofN-cyano-S-methyl-N-[α-(2-pyridyl)orthomethylbenzyl]isothiourea preparedin (a), 30 ml of 20% solution of methylamine in ethanol and 70 ml ofethanol was prepared and reacted at room temperature overnight. Thereaction solution was concentrated under a reduced pressure. The residuewas recrystallized from ethyl acetate to produce 4.7 g of the subjectmaterial, N-cyano-N'-methyl-N-[α-(2-pyridyl)orthomethylbenzyl]guanidine(yield: 85.0%).

Melting point: 187°-9° C.

Elementary analysis of the compound having the presumed formula C₁₆ H₁₇N₅ gave:

    ______________________________________                                                   C          H      N                                                ______________________________________                                        Calculated (%):                                                                            68.78        6.13   25.07                                        Found (%):   68.83        6.01   25.26                                        ______________________________________                                    

(2) Alpha-(2-pyridyl)orthomethylbenzylamine in amount of 1.8 g (0.01mol) and N-cyano-S,N'-dimethylisothiourea in amount of 1.3 g (0.01 mol)were dissolved in 50 ml of acetonitrile. The whole was reacted underheating for 10-15 hours. The reaction solution was then concentratedunder reduced pressure. The residue was recrystallized from ethylacetate to produce 1.6 g of the subject material,N-cyano-N'-methyl-N-[α-(2-pyridyl)orthomethylbenzyl]guanidine (yield:59.0%).

Melting point: 187°-9° C.

Elementary analysis of the compound having the presumed formula C₁₆ H₁₇N₅ gave:

    ______________________________________                                                   C          H      N                                                ______________________________________                                        Calculated (%):                                                                            68.78        6.13   25.07                                        Found (%):   68.81        6.05   25.20                                        ______________________________________                                    

EXAMPLES 2-107

Examples 2-107 were achieved according to the process for thepreparation as described in Example 1 (1) via isothiourea derivatives.Tables 7 and 8 show respectively melting point, yield (%) and elementaryanalysis of the resulting isothiourea derivatives and the compounds ofthis invention.

In Table 7, the general formula: ##STR8## represents the formula whereinp is 0 and Y is methylthio group in the formula (V) hereinbeforementioned.

In Table 8, the general formula: ##STR9## represents the formula whereinp is 0 in the formula (I).

                                      TABLE 7                                     __________________________________________________________________________     ##STR10##                                                                                                         Elementary Analysis                                          Melting          Upper line: Calcd.                                           Point    Molecular                                                                             Lower line: Found                        Ex.                                                                              A         B      (°C.)                                                                       Yield                                                                             Formula C   H  N                                 __________________________________________________________________________        ##STR11##                                                                              2-pyridyl                                                                            166-168                                                                            63.5                                                                              C.sub.16 H.sub.16 N.sub.4 S                                                           64.83 64.87                                                                       5.44 5.26                                                                        18.90 19.01                       3                                                                                 ##STR12##                                                                              2-pyridyl                                                                            148-149                                                                            76.7                                                                              C.sub.16 H.sub.16 N.sub.4 S                                                           64.83 65.05                                                                       5.44 5.36                                                                        18.90 18.91                       4                                                                                 ##STR13##                                                                              2-pyridyl                                                                            119-120                                                                            71.7                                                                              C.sub.15 H.sub.13 N.sub.4 SCl                                                         56.87 56.60                                                                       4.10 4.09                                                                        17.69 17.05                       5                                                                                 ##STR14##                                                                              2-pyridyl                                                                            205-206                                                                            80.1                                                                              C.sub.15 H.sub.13 N.sub.4 SCl                                                         56.87 56.65                                                                       4.10 3.94                                                                        17.69 17.45                       6                                                                                 ##STR15##                                                                              2-pyridyl                                                                            121-122                                                                            85.5                                                                              C.sub.15 H.sub.13 N.sub.4 SCl                                                         56.87 56.79                                                                       4.10 4.06                                                                        17.69 17.50                       7                                                                                 ##STR16##                                                                              2-pyridyl                                                                            118-119                                                                            55.3                                                                              C.sub.15 H.sub.12 N.sub.4 SCl.sub.2                                                   51.28 51.09                                                                       3.42 3.29                                                                        15.95 15.62                       8                                                                                 ##STR17##                                                                              2-pyridyl                                                                            126-128                                                                            64.5                                                                              C.sub.16 H.sub.16 N.sub.4 OS                                                          61.53 61.43                                                                       5.16 4.98                                                                        17.94 17.47                       9                                                                                 ##STR18##                                                                              2-pyridyl                                                                            162-163                                                                            84.0                                                                              C.sub.16 H.sub.16 N.sub.4 OS                                                          61.53 61.90                                                                       5.16 5.03                                                                        17.94 17.79                       10                                                                                ##STR19##                                                                              2-pyridyl                                                                            151-152                                                                            70.0                                                                              C.sub.16 H.sub.16 N.sub.4 OS                                                          61.53 61.60                                                                       5.16 5.05                                                                        17.94 18.08                       11                                                                                ##STR20##                                                                              2-pyridyl                                                                            155-156                                                                            88.0                                                                              C.sub.17 H.sub.18 N.sub.4 O.sub.2 S                                                   59.64 59.76                                                                       5.30 5.24                                                                        16.37 16.77                       12                                                                                ##STR21##                                                                              2-pyridyl                                                                            117-118                                                                            86.5                                                                              C.sub.17 H.sub.18 N.sub.4 OS                                                          62.56 63.05                                                                       5.56 5.42                                                                        17.17 17.23                       13                                                                                ##STR22##                                                                              2-pyridyl                                                                            138-139                                                                            87.5                                                                              C.sub.18 H.sub.20 N.sub.4 OS                                                          63.51 63.54                                                                       5.92 5.84                                                                        16.46 15.96                       14                                                                                ##STR23##                                                                              2-pyridyl                                                                            103-104                                                                            68.8                                                                              C.sub.16 H.sub.16 N.sub.4 S.sub.2                                                     58.53 58.71                                                                       4.91 4.69                                                                        17.07 17.41                       15                                                                                ##STR24##                                                                              2-pyridyl                                                                            139-140                                                                            71.1                                                                              C.sub.16 H.sub.16 N.sub.4 O.sub.2 S.sub.2                                             53.33 53.14                                                                       4.48 4.19                                                                        15.55 15.43                       16                                                                                ##STR25##                                                                              2-pyridyl                                                                            163-164                                                                            68.1                                                                              C.sub.16 H.sub.13 N.sub.4 F.sub.3 S                                                   54.86 54.88                                                                       3.74 3.76                                                                        16.00 16.12                       17                                                                                ##STR26##                                                                               ##STR27##                                                                           182-183                                                                            65.5                                                                              C.sub.15 H.sub.14 N.sub.4 OS                                                          60.40 60.73                                                                       4.70 4.58                                                                        18.79 18.82                       18                                                                                ##STR28##                                                                              2-pyridyl                                                                            116-118                                                                            70.0                                                                              C.sub.13 H.sub.12 N.sub.4 OS                                                          57.33 57.50                                                                       4.44 4.18                                                                        20.57 20.54                       19                                                                                ##STR29##                                                                              2-pyridyl                                                                            104-106                                                                            56.0                                                                              C.sub.13 H.sub.12 N.sub.4 S.sub.2                                                     54.13 54.43                                                                       4.19 4.18                                                                        19.43 19.72                       20                                                                                ##STR30##                                                                              2-pyridyl                                                                            140-143                                                                            73.3                                                                              C.sub.15 H.sub.20 N.sub.4 S                                                           62.46 62.82                                                                       6.98 6.99                                                                        19.43 19.20                       21                                                                                ##STR31##                                                                               ##STR32##                                                                           150-152                                                                            46.3                                                                              C.sub.16 H.sub.15 N.sub.3 S                                                           68.29 68.30                                                                       5.38 5.52                                                                        14.94 14.87                       22                                                                                ##STR33##                                                                              2-pyridyl                                                                            152-153                                                                            60.1                                                                              C.sub.17 H.sub.18 N.sub.4 OS                                                          62.56 62.90                                                                       5.56 5.57                                                                        17.17 17.11                       __________________________________________________________________________

                                      TABLE 8                                     __________________________________________________________________________     ##STR34##                                                                                                                     Elementary Analysis                                         Melting           Upper line: Calcd.                                          Point     Molecular                                                                             Lower line: Found            Ex.                                                                              A         B      R          (°C.)                                                                       Yield                                                                              Formula C    H   N                   __________________________________________________________________________     2                                                                                ##STR35##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          132-133                                                                            81.0 C.sub.17 H.sub.19 N.sub.5                                                             69.59 69.98                                                                        6.52 6.53                                                                         23.87 23.76          3                                                                                ##STR36##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      147-149                                                                            79.5 C.sub.18 H.sub.19 N.sub.5                                                             70.79 71.21                                                                        6.27 6.16                                                                         22.93 22.96          4                                                                                ##STR37##                                                                              2-pyridyl                                                                             ##STR38## 115-117                                                                            86.0 C.sub.22 H.sub.30                                                                     69.80 70.12                                                                        7.99 8.09                                                                         22.20 22.30          5                                                                                ##STR39##                                                                              2-pyridyl                                                                             ##STR40## 171-172                                                                            55.5 C.sub.22 H.sub.28 N.sub.6                                                             70.17 70.58                                                                        7.49 7.56                                                                         22.32 22.54          6                                                                                ##STR41##                                                                              2-pyridyl                                                                            CH.sub.3   172-174                                                                            76.0 C.sub.16 H.sub.17 N.sub.5                                                             68.78 69.09                                                                        6.13 6.14                                                                         25.07 25.07          7                                                                                ##STR42##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          145-147                                                                            83.1 C.sub.17 H.sub.19 N.sub.5                                                             69.59 69.46                                                                        6.52 6.63                                                                         23.87 23.68          8                                                                                ##STR43##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      112-114                                                                            75.5 C.sub.18 H.sub.19 N.sub.5                                                             70.79 70.78                                                                        6.27 6.38                                                                         22.93 22.81          9                                                                                ##STR44##                                                                              2-pyridyl                                                                             ##STR45## 100-102                                                                            47.4 C.sub.22 H.sub.28 N.sub.6                                                             70.19 70.38                                                                        7.49 7.67                                                                         22.32 22.43         10                                                                                ##STR46##                                                                              2-pyridyl                                                                            CH.sub.3   171-172                                                                            95.9 C.sub.16 H.sub.17 N.sub.5                                                             68.78 68.97                                                                        6.13 6.30                                                                         25.07 24.95         11                                                                                ##STR47##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          153-154                                                                            87.5 C.sub.17 H.sub.19 N.sub.5                                                             69.59 69.81                                                                        6.52 6.50                                                                         23.87 23.85         12                                                                                ##STR48##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      144-145                                                                            88.0 C.sub.18 H.sub.19 N.sub.5                                                             70.79 70.83                                                                        6.27 6.44                                                                         22.93 22.83         13                                                                                ##STR49##                                                                              2-pyridyl                                                                             ##STR50##  84-85                                                                             67.7 C.sub.22 H.sub.30 N.sub.6                                                             69.80 69.78                                                                         7.99 8.06                                                                        22.20 22.09         14                                                                                ##STR51##                                                                              2-pyridyl                                                                             ##STR52## 113-115                                                                            87.4 C.sub.22 H.sub.28 N.sub.6                                                             70.17 69.94                                                                        7.49 7.54                                                                         22.32 22.29         15                                                                                ##STR53##                                                                              2-pyridyl                                                                            CH.sub.3   210-211                                                                            89.3 C.sub.15 H.sub.14 N.sub.5                                                             60.10 60.15                                                                        4.67 4.56                                                                         23.40 23.34         16                                                                                ##STR54##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          176-177                                                                            84.9 C.sub.16 H.sub.16 N.sub.5                                                             61.24 61.28                                                                        5.10 4.89                                                                         22.33 22.43         17                                                                                ##STR55##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      144-145                                                                            81.7 C.sub.17 H.sub.16 N.sub.5                                                             62.27 62.54                                                                        4.92 4.72                                                                         21.51 21.74         18                                                                                ##STR56##                                                                              2-pyridyl                                                                             ##STR57## 103-104                                                                            90.1 C.sub.21 H.sub.27 N.sub.6                                                             63.24 63.16                                                                        6.77 6.88                                                                         21.08 21.01         19                                                                                ##STR58##                                                                              2-pyridyl                                                                             ##STR59## 169-172.5                                                                          70.3 C.sub.21 H.sub.25 N.sub.6                                                             63.56 63.56                                                                        6.30 6.20                                                                         21.18 21.24         20                                                                                ##STR60##                                                                              2-pyridyl                                                                            CH.sub.3   194-195                                                                            84.2 C.sub.15 H.sub.14 N.sub.5                                                             60.10 60.05                                                                        4.67 4.62                                                                         23.40 23.40         21                                                                                ##STR61##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          153-155                                                                            92.9 C.sub.16 H.sub.16 N.sub.5                                                             61.24 61.11                                                                        5.10 5.14                                                                         22.33 22.25         22                                                                                ##STR62##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      136-137                                                                            87.5 C.sub.17 H.sub.16 N.sub.5                                                             62.27 61.90                                                                        4.92 4.80                                                                         21.51 20.87         23                                                                                ##STR63##                                                                              2-pyridyl                                                                             ##STR64##  80-84                                                                             69.8 C.sub.21 H.sub.27 N.sub.6                                                             63.24 63.30                                                                        6.77 6.79                                                                         21.08 21.22         24                                                                                ##STR65##                                                                              2-pyridyl                                                                             ##STR66## 117-118                                                                            63.9 C.sub.21 H.sub.25 N.sub.6                                                             63.56 63.76                                                                        6.30 6.55                                                                         21.18 20.89         25                                                                                ##STR67##                                                                              2-pyridyl                                                                            CH.sub.3   180-181                                                                            96.2 C.sub.15 H.sub.14 N.sub.5                                                             60.10 59.85                                                                        4.67 4.67                                                                         23.40 23.40         26                                                                                ##STR68##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          159-160                                                                            98.6 C.sub.16 H.sub.16 N.sub.5                                                             61.24 61.04                                                                        5.10 5.16                                                                         22.33 21.98         27                                                                                ##STR69##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                       177 87.5 C.sub. 17 H.sub.16 N.sub.5                                                            62.27 62.43                                                                        4.92 4.84                                                                         21.51 21.36         28                                                                                ##STR70##                                                                              2-pyridyl                                                                             ##STR71## 157-161                                                                            66.1 C.sub.21 H.sub.25 N.sub.6                                                             63.56 63.66                                                                        6.30 6.54                                                                         21.18 20.98         29                                                                                ##STR72##                                                                              2-pyridyl                                                                            CH.sub.3   217-218                                                                            81.5 C.sub.15 H.sub.13 N.sub.5                                                     Cl.sub.2                                                                              53.89 54.04                                                                        3.89 4.13                                                                         20.96 20.32         30                                                                                ##STR73##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          137-139                                                                            88.1 C.sub.16 H.sub.15 N.sub.5                                                     Cl.sub.2                                                                              55.17 55.09                                                                        4.31 4.30                                                                         20.11 19.91         31                                                                                ##STR74##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      142-144                                                                            70.7 C.sub.17 H.sub.15 N.sub.5                                                     Cl.sub.2                                                                              56.67 56.57                                                                        4.17 4.12                                                                         19.44 19.35         32                                                                                ##STR75##                                                                              2-pyridyl                                                                             ##STR76##  85-90                                                                             44.6 C.sub.17 H.sub.26 N.sub.6                                                     Cl.sub.2                                                                              58.20 58.26                                                                        6.00 5.97                                                                         19.39 19.35         33                                                                                ##STR77##                                                                              2-pyridyl                                                                             ##STR78## 130-136                                                                            75.5 C.sub.21 H.sub.24 N.sub.6                                                     Cl.sub.2                                                                              58.47 58.65                                                                        5.57 5.62                                                                         19.49 19.36         34                                                                                ##STR79##                                                                              2-pyridyl                                                                            CH.sub.3   173-174                                                                            78.2 C.sub.16 H.sub.17 N.sub.5                                                             65.06 65.36                                                                        5.80 5.81                                                                         23.72 23.70         35                                                                                ##STR80##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          121-122                                                                            64.6 C.sub.17 H.sub.19 N.sub.5                                                             66.00 66.17                                                                        6.19 6.34                                                                         22.64 22.63         36                                                                                ##STR81##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      118-119                                                                            72.0 C.sub.18 H.sub.19 N.sub.5                                                             67.27 67.21                                                                        5.96 6.02                                                                         21.79 21.74         37                                                                                ##STR82##                                                                              2-pyridyl                                                                             ##STR83##  73-74                                                                             41.2 C.sub.22 H.sub.30 N.sub.6                                                             66.97 66.91                                                                        7.67 7.84                                                                         21.30 21.22         38                                                                                ##STR84##                                                                              2-pyridyl                                                                             ##STR85## 136-138                                                                            54.1 C.sub.22 H.sub.28 N.sub.6                                                             67.32 67.56                                                                        7.19 7.43                                                                         21.41 21.20         39                                                                                ##STR86##                                                                              2-pyridyl                                                                            CH.sub.3   149-150                                                                            71.9 C.sub.16 H.sub.17 N.sub.5                                                             65.06 65.27                                                                        5.80 5.79                                                                         23.72 23.91         40                                                                                ##STR87##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          115-116                                                                            74.9 C.sub. 17 H.sub.19 N.sub.5                                                            66.00 66.22                                                                        6.19 6.17                                                                         22.64 22.87         41                                                                                ##STR88##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                       99-100                                                                            60.3 C.sub.18 H.sub.19 N.sub.5                                                             67.27 67.72                                                                        5.96 5.85                                                                         21.79 21.94         42                                                                                ##STR89##                                                                              2-pyridyl                                                                             ##STR90##  85-86                                                                             64.9 C.sub.22 H.sub.30 N.sub.6                                                             66.97 67.04                                                                        7.67 7.74                                                                         21.30 21.38         43                                                                                ##STR91##                                                                              2-pyridyl                                                                             ##STR92## 142-143                                                                            22.0 C.sub.22 H.sub.28 N.sub.6                                                             67.32 67.40                                                                        7.19 7.14                                                                         21.41 21.54         44                                                                                ##STR93##                                                                              2-pyridyl                                                                            CH.sub.3   187-188                                                                            74.0 C.sub.16 H.sub.17 N.sub.5                                                             65.06 65.59                                                                         5.80 6.03                                                                        23.72 23.48         45                                                                                ##STR94##                                                                              2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          144-145                                                                            84.9 C.sub.17 H.sub.19 N.sub.5                                                             66.00 66.05                                                                        6.19 6.12                                                                         22.64 22.52         46                                                                                ##STR95##                                                                              2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      139-140                                                                            70.0 C.sub.18 H.sub.19 N.sub.5                                                             67.27 67.22                                                                        5.96 5.67                                                                         21.79 21.83         47                                                                                ##STR96##                                                                              2-pyridyl                                                                             ##STR97##  74-75                                                                             58.6 C.sub.22 H.sub.30 N.sub.6                                                             66.97 67.22                                                                        7.67 7.68                                                                         21.30 21.35         48                                                                                ##STR98##                                                                              2-pyridyl                                                                             ##STR99## 134-135                                                                            46.2 C.sub.22 H.sub.28 N.sub.6                                                             67.32 67.61                                                                        7.19 7.15                                                                         21.41 21.42         49                                                                                ##STR100##                                                                             2-pyridyl                                                                            CH.sub.3   161-162                                                                            86.3 C.sub.17 H.sub.19 N.sub.5                                                     O.sub.2 62.75 62.44                                                                        5.89 5.52                                                                         21.53 21.51         50                                                                                ##STR101##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          154-155                                                                            80.7 C.sub.18 H.sub.21 N.sub.5                                                     O.sub.2 63.70 63.79                                                                        6.24 6.20                                                                         20.14 20.58         51                                                                                ##STR102##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      102-103                                                                            64.3 C.sub.19 H.sub.21 N.sub.5                                                     O.sub.2 64.94 65.22                                                                        6.02 6.12                                                                         19.93 19.92         52                                                                                ##STR103##                                                                             2-pyridyl                                                                             ##STR104##                                                                              103-104                                                                            49.4 C.sub.23 H.sub.32 N.sub.6                                                     O.sub.2 65.07 65.39                                                                        7.60 7.64                                                                         19.80 20.13         53                                                                                ##STR105##                                                                             2-pyridyl                                                                             ##STR106##                                                                              141-143                                                                            29.2 C.sub.23 H.sub.30 N.sub.6                                                     O.sub.2 65.38 65.81                                                                        7.16 7.18                                                                         19.89 20.30         54                                                                                ##STR107##                                                                             2-pyridyl                                                                            CH.sub.3   149-150                                                                            73.8 C.sub.17 H.sub.19 N.sub.5                                                             66.00 66.32                                                                        6.19 6.07                                                                         22.64 22.37         55                                                                                ##STR108##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          139-140                                                                            80.7 C.sub.18 H.sub.21 N.sub.5                                                             66.85 66.35                                                                        6.55 6.59                                                                         21.66 21.37         56                                                                                ##STR109##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      112-113                                                                            73.9 C.sub.19 H.sub.21 N.sub.5                                                             68.04 68.34                                                                        6.31 6.16                                                                         20.88 20.35         57                                                                                ##STR110##                                                                             2-pyridyl                                                                             ##STR111##                                                                               84-85                                                                             59.0 C.sub.23 H.sub.32 N.sub.6                                                             67.62 68.00                                                                        7.90 8.09                                                                         20.57 20.72         58                                                                                ##STR112##                                                                             2-pyridyl                                                                             ##STR113##                                                                              121-123                                                                            70.6 C.sub.23 H.sub.30 N.sub.6                                                             67.85 68.34                                                                        7.44 7.48                                                                         20.67 20.80         59                                                                                ##STR114##                                                                             2-pyridyl                                                                            CH.sub.3   148-149                                                                            69.5 C.sub.18 H.sub.21 N.sub.5                                                             66.85 67.25                                                                        6.55 6.52                                                                         21.66 21.88         60                                                                                ##STR115##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          141-142                                                                            72.6 C.sub.19 H.sub.23 N.sub.5                                                             67.63 67.55                                                                        6.87 6.75                                                                         20.76 20.39         61                                                                                ##STR116##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      120-121                                                                            62.4 C.sub.20 H.sub. 23 N.sub.5                                                            68.74 68.59                                                                        6.63 6.56                                                                         20.04 20.00         62                                                                                ##STR117##                                                                             2-pyridyl                                                                             ##STR118##                                                                              100-101                                                                            83.7 C.sub.24 H.sub.34 N.sub.6                                                             68.21 68.33                                                                        8.11 8.35                                                                         19.89 20.10         63                                                                                ##STR119##                                                                             2-pyridyl                                                                             ##STR120##                                                                              134-136                                                                            45.3 C.sub.24 H.sub.32 N.sub.6                                                             68.54 69.15                                                                        7.67 7.76                                                                         19.99 20.49         64                                                                                ##STR121##                                                                             2-pyridyl                                                                            CH.sub.3   206-207                                                                            65.4 C.sub.16 H.sub.17 N.sub.5                                                             61.72 62.01                                                                        5.50 5.39                                                                         22.50 22.52         65                                                                                ##STR122##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          132-133                                                                            66.6 C.sub.17 H.sub.19 N.sub.5                                                             62.75 62.55                                                                        5.89  5.66                                                                        21.53 21.38         66                                                                                ##STR123##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      111-112                                                                            68.1 C.sub.18 H.sub.19 N.sub.5                                                             64.08 64.28                                                                        5.68 5.59                                                                         20.76 20.66         67                                                                                ##STR124##                                                                             2-pyridyl                                                                             ##STR125##                                                                               88-89                                                                             52.8 C.sub.22 H.sub.30 N.sub.6                                                             64.36 64.68                                                                        7.37 7.61                                                                         20.47 20.26         68                                                                                ##STR126##                                                                             2-pyridyl                                                                             ##STR127##                                                                              132-133                                                                            64.3 C.sub.22 H.sub.28 N.sub.6                                                             64.68 64.81                                                                        6.91 6.82                                                                         20.58 20.55         69                                                                                ##STR128##                                                                             2-pyridyl                                                                            CH.sub.3   152-153                                                                            67.2 C.sub.16 H.sub.17 N.sub.5                                                     O.sub.2 S                                                                             55.97 55.76                                                                        4.99 4.74                                                                         20.40 20.27         70                                                                                ##STR129##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          109-110                                                                            62.5 C.sub.17 H.sub.19 N.sub.5                                                     O.sub.2 S                                                                             57.13 57.18                                                                        5.36 5.65                                                                         19.60 19.68         71                                                                                ##STR130##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      124-125                                                                            64.5 C.sub.18 H.sub.19 N.sub.5                                                     O.sub.2 S                                                                             58.53 58.75                                                                        5.19 5.08                                                                         18.96 18.97         72                                                                                ##STR131##                                                                             2-pyridyl                                                                             ##STR132##                                                                              127-129                                                                            28.2 C.sub.22 H.sub.30 N.sub.6                                                     O.sub.2 S                                                                             57.37 57.36                                                                        7.00 7.11                                                                         18.25 18.05         73                                                                                ##STR133##                                                                             2-pyridyl                                                                             ##STR134##                                                                              155-156                                                                            29.2 C.sub.22 H.sub.28 N.sub.6                                                     O.sub.2 S                                                                             59.98 60.17                                                                        6.41 6.53                                                                         19.08 18.69         74                                                                                ##STR135##                                                                             2-pyridyl                                                                            CH.sub.3   175-176                                                                            63.0 C.sub.16 H.sub.14 N.sub.5                                                     F.sub.3 57.65 57.54                                                                        4.23 4.25                                                                         21.01 21.00         75                                                                                ##STR136##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          158-159                                                                            70.7 C.sub.17 H.sub.16 N.sub.5                                                     F.sub.3 58.78 58.58                                                                        4.64 4.64                                                                         20.16 20.20         76                                                                                ##STR137##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      115-116                                                                            64.3 C.sub.18 H.sub.16 N.sub.5                                                     F.sub.3 60.16 60.07                                                                        4.49 4.50                                                                         19.49 19.53         77                                                                                ##STR138##                                                                             2-pyridyl                                                                             ##STR139##                                                                               74-75                                                                             39.6 C.sub.22 H.sub.27 N.sub.6                                                     F.sub.3 61.09 61.28                                                                        6.29 6.08                                                                         19.43 19.56         78                                                                                ##STR140##                                                                             2-pyridyl                                                                             ##STR141##                                                                              137-138                                                                            60.6 C.sub.22 H.sub.25 N.sub.6                                                     F.sub.3 61.38 61.36                                                                        5.84 5.87                                                                         19.52 19.60         79                                                                                ##STR142##                                                                              ##STR143##                                                                          CH.sub.3   178-181                                                                            84.9 C.sub.15 H.sub.15 N.sub.5                                                             64.06 63.80                                                                        5.34 5.08                                                                         24.91 24.77         80                                                                                ##STR144##                                                                              ##STR145##                                                                          C.sub.2 H.sub.5                                                                           97-98                                                                             58.6 C.sub.16 H.sub.17 N.sub.5                                                             65.08 64.92                                                                        5.76 5.60                                                                         23.73 23.49         81                                                                                ##STR146##                                                                              ##STR147##                                                                          CH.sub.2 CHCH.sub.2                                                                      167-168                                                                            67.9 C.sub.17 H.sub.17 N.sub.5                                                             66.45 66.80                                                                        5.54 5.38                                                                         22.80 22.76         82                                                                                ##STR148##                                                                              ##STR149##                                                                           ##STR150##                                                                              128-129                                                                            70.6 C.sub.21 H.sub.28 N.sub.6                                                             66.32 66.35                                                                        7.37 7.44                                                                         22.11 22.01         83                                                                                ##STR151##                                                                              ##STR152##                                                                           ##STR153##                                                                              185-187                                                                            34.9 C.sub.21 H.sub.26 N.sub.6                                                             66.64 66.31                                                                        6.92 6.93                                                                         22.21 21.91         84                                                                                ##STR154##                                                                             2-pyridyl                                                                            CH.sub.3   141-143                                                                            72.8 C.sub.13 H.sub.12 N.sub.5                                                             61.40 61.49                                                                        4.75 5.03                                                                         27.54 27.76         85                                                                                ##STR155##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          131-133                                                                            72.6 C.sub.14 H.sub.15 N.sub.5                                                             62.43 62.74                                                                        5.61 5.66                                                                         26.00 26.30         86                                                                                ##STR156##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      129-130                                                                            87.0 C.sub.15 H.sub.15 N.sub.5                                                             64.03 64.30                                                                        5.37 5.66                                                                         24.90 25.35         87                                                                                ##STR157##                                                                             2-pyridyl                                                                            CH.sub.3   137-139                                                                            66.0 C.sub.13 H.sub.13 N.sub.5                                                             57.53 57.87                                                                        4.82 4.85                                                                         25.81 25.77         88                                                                                ##STR158##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          161-163                                                                            64.9 C.sub.14 H.sub.15 N.sub.5                                                             58.91 58.95                                                                        5.29 5.16                                                                         24.54 24.26         89                                                                                ##STR159##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      123-125                                                                            73.9 C.sub.15 H.sub.15 N.sub.5                                                             60.57 60.90                                                                        5.08 4.97                                                                         23.55 23.24         90                                                                                ##STR160##                                                                             2-pyridyl                                                                             ##STR161##                                                                              112-114                                                                            53.1 C.sub.19 H.sub.24 N.sub.6                                                             61.92 61.91                                                                        6.56 6.23                                                                         22.81 22.61         91                                                                                ##STR162##                                                                             2-pyridyl                                                                            CH.sub.3   195-197                                                                            76.1 C.sub.15 H.sub.21 N.sub.5                                                             66.38 66.23                                                                        7.80 7.90                                                                         25.81 25.74         92                                                                                ##STR163##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          153-155                                                                            78.5 C.sub.16 H.sub.23 N.sub.5                                                             67.33 67.48                                                                        8.12 8.18                                                                         24.54 24.56         93                                                                                ##STR164##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      100-102                                                                            53.6 C.sub.17 H.sub.23 N.sub.5                                                             68.65 68.89                                                                        7.79 8.07                                                                         23.55 23.72         94                                                                                ##STR165##                                                                             2-pyridyl                                                                             ##STR166##                                                                              148-151                                                                            41.9 C.sub.21 H.sub.32 N.sub.6                                                             68.43 68.28                                                                        8.75 8.90                                                                         22.80 22.65         95                                                                                ##STR167##                                                                              ##STR168##                                                                          CH.sub.3   147-150                                                                            78.5 C.sub.16 H.sub.16 N.sub.4                                                             72.70 73.01                                                                        6.10 6.05                                                                         21.20 21.06         96                                                                                ##STR169##                                                                              ##STR170##                                                                          C.sub.2 H.sub.5                                                                          145- 146                                                                           82.2 C.sub.17 H.sub.18 N.sub.4                                                             73.34 73.47                                                                        6.53 6.73                                                                         20.13 20.13         97                                                                                ##STR171##                                                                              ##STR172##                                                                          CH.sub.2 CHCH.sub.2                                                                      149-150                                                                            78.8 C.sub.18 H.sub.18 N.sub.4                                                             74.45 74.78                                                                        6.25 6.11                                                                         19.30 19.20         98                                                                                ##STR173##                                                                              ##STR174##                                                                           ##STR175##                                                                              122-124                                                                            82.6 C.sub.22 H.sub.29 N.sub.5                                                             72.69 73.21                                                                        8.04 7.95                                                                         19.27 19.22         99                                                                                ##STR176##                                                                              ##STR177##                                                                           ##STR178##                                                                              176-178                                                                            71.2 C.sub.22 H.sub.27 N.sub.5                                                             73.09 73.29                                                                        7.53 7.49                                                                         19.38 19.24         100                                                                               ##STR179##                                                                             2-pyridyl                                                                            CH.sub.3   192-193                                                                            71.7 C.sub.17 H.sub.19 N.sub.5                                                             66.00                                                                              6.19 6.11                                                                         22.64 22.56         101                                                                               ##STR180##                                                                             2-pyridyl                                                                            C.sub.2 H.sub.5                                                                          136-137                                                                            79.8 C.sub.18 H.sub.21 N.sub.5                                                             66.85 67.12                                                                        6.55 6.53                                                                         21.66 21.72         102                                                                               ##STR181##                                                                             2-pyridyl                                                                            CH.sub.2 CHCH.sub.2                                                                      131-132                                                                            71.3 C.sub.19 H.sub.21 N.sub.5                                                             68.04 68.21                                                                        6.31 6.25                                                                         20.88 20.62         103                                                                               ##STR182##                                                                             2-pyridyl                                                                            n-C.sub.3 H.sub.7                                                                        119-120                                                                            87.3 C.sub.18 H.sub.21 N.sub.5                                                             66.85 67.30                                                                        6.55 6.63                                                                         21.66 21.64         104                                                                               ##STR183##                                                                             2-pyridyl                                                                             ##STR184##                                                                              105-106                                                                            46.6 C.sub.21 H.sub.28 N.sub.6                                                             66.29 66.60                                                                        7.42 7.55                                                                         22.99 22.39         105                                                                               ##STR185##                                                                             2-pyridyl                                                                             ##STR186##                                                                              122-123                                                                            74.4 C.sub.20 H.sub.26 N.sub.6                                                             68.54 68.95                                                                        7.48 7.47                                                                         23.98 23.89         106                                                                               ##STR187##                                                                             2-pyridyl                                                                            n-C.sub.4 H.sub.9                                                                        175-176                                                                            89.0 C.sub.18 H.sub.20 N.sub.5                                                             63.25 63.40                                                                        5.86 5.98                                                                         20.50 20.45         107                                                                               ##STR188##                                                                             2-pyridyl                                                                             ##STR189##                                                                               92-95                                                                             84.2 C.sub.20 H.sub.25 N.sub.5                                                             68.34 68.41                                                                        7.18 7.17                                                                         19.93 19.86         __________________________________________________________________________

EXAMPLE 108

Five grams (0.018 mol) ofN-cyano-N'-[α-(2-pyridyl)benzyl]-S-methylisothiourea and 5 g (0.057 mol)of N,N-dimethylethylenediamine were dissolved in 100 ml of ethanol, andthe whole was reacted under reflux for 10-15 hours. The reactionsolution was concentrated under a reduced pressure. The residue waswashed with water, followed by recrystalizing from ethyl acetate toproduce 3.4 g ofN-cyano-N'-(2-dimethylamino)ethyl-N-[α-(2-pyridyl)benzyl]guanidine(yield: 58.7%).

Melting point: 142°-4° C.

Elementary analysis (%) for C₁₈ H₂₂ N₆ :

    ______________________________________                                                 C           H      N                                                 ______________________________________                                        Calculated:                                                                              67.04         6.89   26.07                                         Found:     67.09         6.97   25.96                                         ______________________________________                                    

EXAMPLES 109-123

The following Table 9 shows the compounds which were prepared using theprocedures similar to Example 108.

In Table 9 Part I, the general formula: ##STR190## represents theformula wherein A is phenyl, B is pyridyl, and p is 0 in the formula (I)hereinbefore mentioned.

In Table 9 Part II, the general formula: ##STR191## represents theformula wherein A is phenyl, B is pyridyl, and p is 1 in the formula(I).

                                      TABLE 9                                     __________________________________________________________________________                                              Elementary Analysis                                            Melting        Upper line: Calcd.                                             Point    Molecular                                                                           Lower line: Found                   Ex.                                                                              B    R           X      (°C.)                                                                       Yield                                                                             Formula                                                                             C   H  N                            __________________________________________________________________________     ##STR192##                                                                   109                                                                              2-pyridyl                                                                           ##STR193##        151-152                                                                            82.5                                                                              C.sub.20 H.sub.26 N.sub.6                                                           68.53 68.76                                                                       7.49 7.56                                                                        23.98 23.97                  110                                                                              2-pyridyl                                                                           ##STR194##        143  86.0                                                                              C.sub.19 H.sub.24 N.sub.6                                                           67.83 67.87                                                                       7.19 7.47                                                                        24.98 24.11                  111                                                                              2-pyridyl                                                                           ##STR195##        84-85                                                                              58.0                                                                              C.sub.21 H.sub.28 N.sub.6                                                            69.18 69.21                                                                      7.76 7.81                                                                        23.06 22.89                  112                                                                              2-pyridyl                                                                           ##STR196##        136-137                                                                            67.5                                                                              C.sub.21 H.sub.26 N.sub.6                                                           69.58 70.15                                                                       7.23 7.44                                                                        23.19 23.17                  113                                                                              2-pyridyl                                                                           ##STR197##        142-143                                                                            75.8                                                                              C.sub.21 H.sub.26 N.sub.6 O                                                         66.64 67.07                                                                       6.92 6.97                                                                        22.21 22.72                  114                                                                              3-pyridyl                                                                           ##STR198##        97-98                                                                              64.8                                                                              C.sub.21 H.sub.28 N.sub.6                                                           69.19 69.24                                                                       7.74 7.70                                                                        23.06 23.12                  115                                                                              3-pyridyl                                                                           ##STR199##        148-150                                                                            53.1                                                                              C.sub.21 H.sub.21 N.sub.6                                                           69.58 69.36                                                                       7.23 7.22                                                                        23.19 23.51                  116                                                                              4-pyridyl                                                                           ##STR200##        133-135                                                                            51.1                                                                              C.sub.21 H.sub.28 N.sub.6                                                           69.19 69.12                                                                       7.74 7.87                                                                        23.06 23.01                  117                                                                              4-pyridyl                                                                           ##STR201##        166-168                                                                            44.05                                                                             C.sub.21 H.sub.21 N.sub.6                                                           69.58 69.80                                                                       7.23 7.12                                                                        23.19 23.24                  118                                                                              2-pyridyl                                                                           ##STR202##        155-158                                                                            73.0                                                                              C.sub.20 H.sub.24 N.sub.6                                                           68.92 69.36                                                                       6.96 7.02                                                                        24.12 24.12                  119                                                                              2-pyridyl                                                                           ##STR203##         99-101                                                                            72.6                                                                              C.sub.23 H.sub.30 N.sub.6                                                           70.72 70.87                                                                       7.76 7.58                                                                        21.52 21.11                   ##STR204##                                                                   120                                                                              2-pyridyl                                                                           ##STR205## CH.sub.2                                                                             104-105                                                                            41.0                                                                              C.sub.22 H.sub.30 N.sub.6                                                           69.81 69.75                                                                       7.99 7.90                                                                        22.20 22.08                  121                                                                              2-pyridyl                                                                           ##STR206## CH.sub.2                                                                             136-138                                                                            40.8                                                                              C.sub.22 H.sub.23 N.sub.6                                                           70.18 70.38                                                                       7.50 7.63                                                                        22.32 22.46                  122                                                                              2-pyridyl                                                                           ##STR207## (CH.sub.2).sub.2 S                                                                   94-95                                                                              47.1                                                                              C.sub.23 H.sub.32 N.sub.6 S                                                         65.06 65.23                                                                       7.60 7.54                                                                        19.79 19.85                  123                                                                              2-pyridyl                                                                           ##STR208## (CH.sub.2).sub.2 S                                                                   130-131                                                                            41.9                                                                              C.sub.23 H.sub.30 N.sub.6 S                                                         65.37 65.48                                                                       7.16 7.36                                                                        19.89 19.11                  __________________________________________________________________________

What is claimed is:
 1. A compound of the formula ##STR209## wherein B is2-, 3- or 4-pyridyl, R represents a group of the formula: ##STR210##wherein R₁ and R₂ are the same or different, and each represent a loweralkyl group, or together form a nitrogen-containing heterocycle of5-member ring or 6-member ring which ring may also contain oxygen ashetero atom, and n is an integer of 1-3, or R represents a group of theformula ##STR211## wherein R₃ is a lower alkyl group, n is an integer of1-3, and m is an integer of 4-5.
 2. A compound according to claim 1wherein B is 2-pyridyl and R is ##STR212##
 3. A compound according toclaim 1 wherein B is 2-pyridyl and R is ##STR213##
 4. A compoundaccording to claim 1 wherein B is 2-pyridyl and R is ##STR214##
 5. Acompound according to claim 1 wherein B is 2-pyridyl and R is ##STR215##6. A compound according to claim 1 wherein B is 2-pyridyl and R is##STR216##
 7. A compound according to claim 1 wherein B is 2-pyridyl andR is ##STR217##
 8. A compound according to claim 1 wherein B is3-pyridyl and R is ##STR218##
 9. A compound according to claim 1 whereinB is 3-pyridyl and R is ##STR219##
 10. A compound according to claim 1wherein B is 4-pyridyl and R is ##STR220##
 11. A compound according toclaim 1 wherein B is 4-pyridyl and R is ##STR221##
 12. A compoundaccording to claim 1 wherein B is 2-pyridyl and R is ##STR222##
 13. Acompound according to claim 1 wherein B is 2-pyridyl and R is ##STR223##